Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720

Marques, Rodolfo Ferreira; Melo, Filipe M. de; Novais, Janaina Tenório; Soares, Irene da Silva; Bargieri, Daniel Youssef; Gimenez, Alba Marina

doi:10.3389/fimmu.2022.910022

Cited by 6 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recombinant MOMP (rMOMP) and EBs were also included as positive controls. CpG-1826 has been reported to promote a Th1 response while Montanide ISA 720 induces a mixed Th1/Th2 response 32 , 33 . Importantly, the combination has been shown to be effective as adjuvants for chlamydial vaccines 34 .…”

Section: Resultsmentioning

confidence: 99%

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen

Hoang-Phou,

Pal,

Slepenkin

et al. 2024

Preprint

View full text Add to dashboard Cite

Chlamydia trachomatisis the most prevalent bacterial sexually transmitted pathogen worldwide. Since chlamydial infection is largely asymptomatic with the potential for serious complications, a preventative vaccine is likely the most viable long-term answer to this public health threat. Cell-free protein synthesis (CFPS) utilizes the cellular protein manufacturing machinery decoupled from the requirement for maintaining cellular viability, offering the potential for flexible, rapid, and de-centralized production of recombinant protein vaccine antigens. Here, we use CFPS to produce the putative chlamydial type three secretion system (T3SS) needle-tip protein, CT584, for use as a vaccine antigen in mouse models. High-speed atomic force microscopy (HS-AFM) imaging and computer simulations confirm that CFPS-produced CT584 retains a native-like structure prior to immunization. Female mice were primed with CT584 adjuvanted with CpG-1826 intranasally (i.n.) or CpG-1826 + Montanide ISA 720 intramuscularly (i.m.), followed four-weeks later by an i.m. boost before respiratory challenge with 104inclusion forming units (IFU) ofChlamydia muridarum. Immunization with CT584 generated robust antibody responses but weak cell mediated immunity and failed to protect against i.n. challenge as demonstrated by body weight loss, increased lungs’ weights and the presence of high numbers of IFUs in the lungs. While CT584 alone may not be the ideal vaccine candidate, the speed and flexibility with which CFPS can be used to produce other potential chlamydial antigens makes it an attractive technique for antigen production.

show abstract

Section: Resultsmentioning

confidence: 99%

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen

Hoang-Phou,

Pal,

Slepenkin

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, this adjuvant induces a potent interferon response and promotes the expression of various cytokines and chemokines. Such an immune response has demonstrated promising results in conferring protection against malaria in murine models; (12) second, it is possible that the antibody response induced after immunisations may have been boosted by the challenge, since MTRAP is expressed in circulating sexual and asexual stages of the parasite. (7,8) Such boost may have had an impact both in magnitude and quality of the antibody response, increasing the ability to reduce ookinete formation.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of the merozoite thrombospondin related anonymous protein (MTRAP) of Plasmodium berghei as a transmission-blocking antigen

Gaitán,

Calit,

Dobrescu

et al. 2024

Mem. Inst. Oswaldo Cruz

Self Cite

View full text Add to dashboard Cite

BACKGROUND Malaria is an infectious disease caused by protozoan parasites belonging to the genus Plasmodium. Human-tohuman transmission depends on a mosquito vector; thus, the interruption of parasite transmission from humans to mosquitoes is an important approach in the fight against malaria. The parasite stages infectious to mosquitoes are the gametocytes, sexual stages that are ingested by the vector during a blood meal and transform into male and female gametes in the midgut. Immunity against sexual stage antigens expressed by gametocytes, gametes, and the zygote formed after fertilisation can interrupt the parasite sexual cycle in the mosquito. This transmission blocking immunity is mediated by specific antibodies ingested during the mosquito blood feed, inhibiting the parasite development in the midgut. Merozoite thrombospondin related anonymous protein (MTRAP) is a merozoite and gametocyte surface protein essential for gamete egress from erythrocytes and for parasite transmission to mosquitoes.OBJECTIVES Here, we evaluated the potential of the P. berghei MTRAP to elicit antibodies with the ability to inhibit gamete fertilisation in vitro.METHODS We expressed a soluble recombinant PbMTRAP and used it to immunise BALB/c mice. The transmission blocking activity of the anti-rPbMTRAP antibodies was tested through in vivo challenge experiments followed by in vitro conversion assays.FINDINGS Immunisations with the rPbMTRAP induced a strong antibody response and the antibodies recognised the native protein by Western Blot and IFA. Anti-rPbMTRAP present in the blood stream of immunised mice partially inhibited gamete conversion into ookinetes.CONCLUSION Our results indicate that antibodies to PbMTRAP may reduce but are not sufficient to completely block transmission.

show abstract

“…Addavax activates the balanced Th1 and Th2 responses and activates both humoral and cell-mediated immunity ( 47 , 48 ). Alhydrogel is primarily the activator of the Th2 response while Montanide ISA 720 activates the innate inflammatory response and recruits antigens-presenting cells at the site of injection ( 49 ) We have analyzed the level of Th1, Th2, and Th17 cytokines in the pooled serum of immunized mice and found the highest level of all the cytokines in the mice sera immunized with PA-FL-Addavax formulation. These increased levels of Th1 and Th2 cytokines represent the multi-dimensional activation of immune response that could correlate to higher protection in the challenged mice.…”

Section: Discussionmentioning

confidence: 99%

Recombinant full-length Bacillus Anthracis protective antigen and its 63 kDa form elicits protective response in formulation with addavax

et al. 2023

View full text Add to dashboard Cite

IntroductionBacillus anthracis is the causative agent for the lethal disease anthrax, primarily affecting animals and humans in close contact with an infected host. The pathogenicity of B. anthracis is attributed to the secreted exotoxins and their outer capsule. The host cell-binding exotoxin component “protective antigen” (PA) is reported to be a potent vaccine candidate. The aim of our study is to produce several PA constructs and analyze their vaccine potential.MethodsWe have designed the various subunit, PA-based recombinant proteins, i.e., full-length Protective antigen (PA-FL), C-terminal 63 kDa fragment (PA63), Protective antigen domain 1-domain 4 chimeras (PA-D1-4) and protective antigen domain 4 (PA-D4) and analyzed their vaccine potential with different human-compatible adjuvants in the mouse model. We have optimized the process and successfully expressed our recombinant antigens as soluble proteins, except full-length PA. All the recombinant antigen formulations with three different adjuvants i.e., Addavax, Alhydrogel, and Montanide ISA 720, were immunized in different mouse groups. The vaccine efficacy of the formulations was analyzed by mouse serum antigen-specific antibody titer, toxin neutralization assay, and survival analysis of mouse groups challenged with a lethal dose of B. anthracis virulent spores.ResultsWe have demonstrated that the PA-FL addavax and PA63 addavax formulations were most effective in protecting spore-challenged mice and serum from the mice immunized with PAFL addavax, PA-FL alhydrogel, PA63 addavax, and PA63 alhydrogel formulations were equivalently efficient in neutralizing the anthrax lethal toxin. The higher levels of serum Th1, Th2, and Th17 cytokines in PA-FL addavax immunized mice correspond to the enhanced protection provided by the formulation in challenged mice.DiscussionWe have demonstrated that the PA-FL addavax and PA63 addavax formulations exhibit equivalent efficiency as vaccine formulation both in a mouse model of anthrax and mammalian cell lines. However, PA63 is a smaller antigen than PA-FL and more importantly, PA63 is expressed as a soluble protein in E. coli, which imparts a translational advantage to PA63-based formulation. Thus, the outcome of our study has significant implications for the development of protective antigen-based vaccine formulations for human use against the lethal disease anthrax.

show abstract

Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720

Cited by 6 publications

References 58 publications

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen

Evaluation in mice of cell-free produced CT584 as a Chlamydia vaccine antigen

Characterisation of the merozoite thrombospondin related anonymous protein (MTRAP) of Plasmodium berghei as a transmission-blocking antigen

Recombinant full-length Bacillus Anthracis protective antigen and its 63 kDa form elicits protective response in formulation with addavax

Contact Info

Product

Resources

About